By Jeffrey T. Jensen, MD, MPH, Editor
SYNOPSIS: In a large, cross-sectional, multicenter study in Italy that evaluated factors predictive of sexual dysfunction, vaginal dryness correlated independently and negatively with each Female Sexual Function Index domain.
SOURCE: Cagnacci A, Venier M, Xholli A, et al. Female sexuality and vaginal health across the menopausal age. Menopause 2020;27:
14-19.
Various factors influence the complex behavior of sexuality. To evaluate changes in female sexuality across the menopausal period, and to test for an association between female sexuality domains and vaginal atrophy (physical findings and symptoms), Cagnacci et al conducted a cross-sectional, multicenter study at 30 outpatient gynecological centers across Italy (the ANGEL study). They recruited healthy women 40 to 55 years of age who reported at least one sexual encounter in the month before enrollment. Key exclusions included virginity, vulvovaginal infections, lichen sclerosus, vaginismus, and vulvodynia. Study staff collected demographic information, data on lifestyle habits, and detailed medical and gynecologic histories, including menopausal symptoms. Eligible participants underwent a pelvic examination; clinicians used vaginal pH > 5, mucosal pallor and dryness, thinning of vaginal rugae, mucosal fragility, and the presence of petechiae as objectives signs indicating vaginal atrophy (VA). They also collected information on subjective symptoms of vaginal dryness, dyspareunia, itching, burning, and dysuria, but did not use these to make the diagnosis of VA. As an objective measure of sexual function, women enrolled in the study completed the Female Sexual Function Index (FSFI). The FSFI provides an overall score and sub-scores for six domains: desire, arousal, lubrication, orgasm, satisfaction, and dyspareunia. Participants respond to each question using a Likert scale from 0 to 6; 0 corresponds to a lack of sexual function and 6 corresponds to full sexual function. The global FSFI score (range 0-36) is calculated as the sum of average scores for each domain (maximum score = 6/domain). The authors used a previously described cut-off score of < 26.55 to define female sexual dysfunction among the study population.
For the analysis, the authors categorized participants into four age groups: late fertile period (40 to 45 years of age); pre-menopause (46 to 48 years); menopausal years (49 to 51 years); and early post-menopausal years (52 to 55 years). They calculated the prevalence of sexual dysfunction (FSFI < 26.55) across the entire sample and compared the prevalence between age groups.
To identify factors independently related to total FSFI score and the individual domains, the researchers used linear regression. The investigators did not specify a sample size, but reported data collected on 518 women.
The overall prevalence of sexual dysfunction (FSFI score < 26.55) in the sample was 70.6%, and this increased from 55% among women aged 40 to 45 years to 82.8% among those aged 52 to 55 years (P < 0.01). Although age, weight, smoking status, sedentary lifestyle, menopausal status, subjective vaginal dryness, dyspareunia, and VA all had an inverse relationship to the FSFI score, only vaginal dryness, postmenopausal status, and weight remained independently associated with FSFI score in the multiple regression model. Only vaginal dryness correlated independently and negatively with each FSFI domain.
Taken together, these results support the idea that the transition from the later reproductive years through menopause is associated with an increasing prevalence of sexual dysfunction, and that vaginal atrophy drives this relationship.
COMMENTARY
We know that vulvovaginal atrophy may accompany an increase in sexual discomfort associated with menopause. This cross-sectional study from Italy provides additional evidence that the prevalence of sexual discomfort rises rapidly during the menopausal transition, and that objective signs of vulvovaginal atrophy are the principal drivers of low scores on all the FSFI domains.
The study has many limitations. The authors sought to evaluate changes in female sexuality over the menopausal transition and to test the association between sexuality and vaginal atrophy. Unfortunately, the cross-sectional design does not allow a hypothesis test. Evaluating a potential association required the use of multiple regression to control for differences between women in the various age groups. Correlations do not infer causality. The study tells us nothing about the actual behavior of the women, nor do we have any information on the potential value of any therapy.
Although we have excellent evidence that hormonal therapy improves symptoms of genital atrophy, the effect of postmenopausal hormonal therapy on sexual function remains an area of ongoing controversy. A recent follow-up study that evaluated sexual activity found no difference in the prevalence of sexual activity following discontinuation of therapy between former participants in the Women’s Health Initiative Study randomized to hormonal therapy (36%) and placebo (34%, P = 0.37).1 However, digging deeper into the data, we see evidence for a beneficial effect of hormone therapy. Compared to placebo (9%), women randomized to active hormonal treatment during the intervention period reported a clinically important and statistically significantly higher decrease (20%) in the frequency of intercourse post-intervention. After discontinuing hormone treatment, they also were more likely to report a decrease in desire (17% vs. 6%), arousal (17% vs. 7%), ability to climax (19% vs. 7%), and satisfaction with sexual activity (17% vs. 8%). Along with those symptoms, they also reported an increase in tightness of vagina (12% vs. 3%) and discomfort with intercourse (15% vs. 3%).
Does local estrogen therapy improve sexual function in postmenopausal women? A recent study by Mitchell and colleagues randomized postmenopausal women to vaginal lubrication gel or vaginal estradiol.2 After 12 weeks of therapy, similar proportions of women in the vaginal estrogen, vaginal gel, and dual placebo reported sexual activity in the past week, and the mean pain scores with sexual activity did not differ between groups. However, significantly more women randomized to the vaginal estradiol reported penetrative sex in the past week and these women showed improvement in vaginal maturation scores and a lowering of vaginal pH, a surrogate for vaginal health. Although the overall comparison did not suggest a decrease in pain between groups, many women did not report a score for sexual pain, presumably because they were not engaging in penetrative sex. More women in the estrogen group reported a score for pain with sexual activity, an important indicator of sexual behavior. My interpretation of the data suggests a positive benefit of estrogen therapy, most likely because of the direct effect of treating vaginal atrophy.
Despite the weakness in study design, the ANGEL study provides some useful information for counseling. Women can expect a decrease in sexual satisfaction as they transition into menopause, and the main driver of this change appears to be vulvovaginal atrophy. Women interested in preserving sexual function should consider local or systemic estrogen therapy.
REFERENCES
- Gass M, Larson J, Cochrane B, et al. Sexual activity and vaginal symptoms in the postintervention phase of the Womenʼs Health Initiative Hormone Therapy Trials. Menopause 2018;25:252-264.
- Mitchell CM, Guthrie KA, Larson J, et al. Sexual frequency and pain in a randomized clinical trial of vaginal estradiol tablets, moisturizer, and placebo in postmenopausal women. Menopause 2019;26:816-822.
In a large, cross-sectional, multicenter study in Italy that evaluated factors predictive of sexual dysfunction, vaginal dryness correlated independently and negatively with each Female Sexual Function Index domain.
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